This project proposes to continue the development of an interstitial microwave antenna array hyperthermia (IMAAH) system for the treatment of cancer. The system permits the implantation of from 1 to 12 antennas (outer diameter 0.8-1.6 mm) via catheters directly into the tumor, and is especially well suited for deep-seated tumors where catheters can be iserted or implanted. Further development of this system should provide the first microwave hyperthermia system able to control the power at different regions in a tumor, hence giving greater flexibility in controlling temperature distributions. The objectives of the current project include: (1) improving the effectiveness of the IMAAH system in clinical studies by improving the antenna design, by adding variable amplitude and phase to each antenna in the array, and by adding a computer based data recording and control system, thereby permitting localized control of temperatures in the tumor; (2) continuing hyperthermia toxicity studies in normal dog brain (acute and chronic studies); (3) conducting clinical studies of single transducer ultrasound (US) hyperthermia and modifying the present US system by adding an assortment of new transducers with different frequencies and diameters; (4) carefully measuring temperature distributions in human tumors and comparing the distributions produced with IMAAH and US systems; (5) studying the thermobiology of interstitial microwave hyperthermia alone, or in combination with radiation or chemotherapy in a transplantable mammary tumor (MTG-B) in the mouse, including aspects of the time-dose relationships, sequencing, thermotolerance, and potentiation by local anesthetics; and (6) investigating the effects of radiation dose rate on the interactions between IMAAH and conventional external beam irradiation on MTG-B in mice. The hyperthermia brain toxicity studies and thermobiology/radiobiology studies should lead to the design of protocols for treating brain tumors and other deep-seated cancers. The long term objective is to ascertain the efficacy of hyperthermia as an adjuvant to radiation and chemotherapy and to compare the efficacy of well-controlled localized hyperthermia against regional heating as a treatment modality in cancer.